Different Cellular and Genetic Basis of Noise-Related Endocochlear Potential Reduction in CBA/J and BALB/cJ Mice

Abstract

The acute and permanent effects of noise exposure on the endocochlear potential (EP) and cochlear lateral wall were evaluated in BALB/cJ (BALB) inbred mice, and compared with CBA/J (CBA) and C57BL/6 (B6) mice. Two-hour exposure to broadband noise (4-45 kHz) at 110 dB SPL leads to a~50 mV reduction in the EP in BALB and CBA, but not B6. EP reduction in BALB and CBA is reliably associated with characteristic acute cellular pathology in stria vascularis and spiral ligament. By 8 weeks after exposure, the EP in CBA mice has returned to normal. In BALBs, however, the EP remains depressed by an average~10 mV, so that permanent EP reduction contributes to permanent threshold shifts in these mice. We recently showed that the CBA noise phenotype in part reflects the influence of a large effect quantitative trait locus on Chr. 18, termed Nirep (Ohlemiller et al., Hear Res 260:47-53, 2010b). While CBA "EP susceptibility" alleles are dominant to those in B6, examination of (B6×BALB) F1 hybrid mice and (F1×BALB) N2 backcross mice revealed that noise-related EP reduction and associated cell pathology in BALBs are inherited in an autosomal recessive manner, and are dependent on multiple genes. Moreover, while N2 mice formed from B6 and CBA retain strong correspondence between acute EP reduction, ligament pathology, and strial pathology, N2s formed from B6 and BALB include subsets that dissociate pathology of ligament and stria. We conclude that the genes and cascades that govern the very similar EP susceptibility phenotypes in BALB and CBA mice need not be the same. BALBs appear to carry alleles that promote more pronounced long term effects of noise on the lateral wall. Separate loci in BALBs may preferentially impact stria versus ligament.

The endocochlear potential as an indicator of reticular lamina integrity after noise exposure in mice

“…1, 2 and 4) indicate that the BALB and CBA mice shown would have exhibited moderate EP reduction, while the EP in the B6 mice would have been normal. This suggests that any EP reduction in older CBA and BALB mice was not due to openings in the reticular lamina, and is in keeping with our previous light microscope analyses at a higher sound level (110 dB SPL) (Ohlemiller and Gagnon, 2007; Ohlemiller et al, 2011a), which showed an intact lamina and little hair cell loss during the exposure.…”

“…Acute EP increases have been attributed to changes in the organ of Corti such as prolonged hair cell depolarization or decreased conductance of transducer channels (Ohlemiller et al, 2016). Acute EP decreases appear attributable to injury to the stria or spiral ligament (Ohlemiller and Gagnon, 2007; Ohlemiller et al, 2011a) or to increased leakiness of the organ of Corti, which may ‘short out’ the EP (Ahmad et al, 2003). Within this framework, the EP may serve either as an indicator of events in the organ of Corti, or as the primary metric of interest, since lateral wall pathology that directly decreases the EP will elevate thresholds independent of any changes in the organ of Corti.…”

“…Following a 2-hr broadband exposure at 110 dB SPL, three inbred mouse strains (C57BL/6J [B6], CBA/J [CBA], BALB/cJ [BALB]) show different phenotypes, such that B6 mice are unaffected, CBA mice show temporary EP reduction, and BALB mice show temporary or permanent EP reduction (Ohlemiller and Gagnon, 2007; Ohlemiller et al, 2010, 2011a). The EP reduction is correlated with histological injury metrics to stria vascularis, spiral ligament, and Reissner’s membrane.…”

“…Intense noise exposure (110 dB SPL, 2 h) differentially affects the EP in three inbred mouse strains (C57BL/6 [B6], CBA/J [CBA], BALB/cJ [BALB]) (Ohlemiller and Gagnon, 2007, Hearing Research 224:34–50; Ohlemiller et al, 2011, JARO 12:45–58). At least for mice older than 3 mos, B6 mice are unaffected, CBA mice show temporary EP reduction, and BALB mice may show temporary or permanent EP reduction.…”

Alpha-synuclein deficiency and efferent nerve degeneration in the mouse cochlea: A possible cause of early-onset presbycusis

“…Several studies have previously demonstrated differences in susceptibility to AHRL between various mice strains (Ohlemiller and Gagnon, 2007;Ohlemiller et al, 2010Ohlemiller et al, , 2011Park et al, 2009). In agreement with these studies, C57 mice showed elevated ABR thresholds at P3mo and P6mo at the 32-kHz tone burst stimulus, but not for the 8-or 16-kHz tone burst or click stimulus.…”